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food source · 3
The word folate comes from the Latin folium, meaning leaf, because folate was first isolated from spinach leaves. Folate is spinach's real strength; its iron, by contrast, is hard to absorb.
Mechanism · What folate does
Folate is the vitamin needed to make DNA and let cells divide, which is why it matters so much before conception and in early pregnancy. Natural folate in food carries a chain of extra glutamate units that must be stripped off in the gut before it can be absorbed, and about 50% of it is available to the body.
Myth · Spinach is not an iron food
Spinach's strengths are folate and vitamin K1, not iron: its iron is harder to absorb than the iron in meat to begin with, and the oxalate in the leaves binds iron and calcium. Blanching and pouring off the water removes part of the oxalate, but folate also dissolves in water and is damaged by heat, so keep the blanching short and lift the leaves out as soon as they wilt.
Broccoli is an everyday source of folate, which sits on the same plant as vitamin C and K1. Folate suffers from long boiling, and stir-frying or steaming keeps more of it.
In practice · How to keep the folate
The folate in broccoli sits on the same plant as vitamin C and K1. It is an everyday source, less dense than dark leafy greens such as spinach. Folate dissolves in water and is damaged by heat, so long boiling loses a lot of it, while stir-frying or steaming keeps more.
Clinical · Why pregnancy calls for folic acid
Preparing for pregnancy cannot rest on this one vegetable. About 50% of the natural folate in food is available to the body; the synthetic folic acid used in fortified foods and supplements is more stable and better absorbed, which is one reason supplementation before conception and in early pregnancy uses the synthetic form.
Lentils are a good plant source of folate: cooked lentils have about 90–180 µg of dietary folate equivalents per 100 g, about 20–45% of an adult's daily need.
Mechanism · Same production line as iron
When the bone marrow makes red blood cells, folate runs cell division (it supplies material for copying DNA) and iron loads hemoglobin into the red cell. Short of folate, the cells come out large and few; short of iron, they come out small and pale. Lentils pack the materials for both steps into one seed, and these are exactly the two that people who eat no meat tend to run short of together.
Numbers · The folate in a serving of lentils
Cooked lentils have about 90–180 µg of dietary folate equivalents per 100 g, about 20–45% of the adult daily need of 400 µg DFE, which matters especially in early pregnancy. Folate dissolves in water and is damaged by heat, so long cooking loses some; with lentil soup, it is best to drink the broth too.
synergy · 3
There are two routes for turning homocysteine back into methionine: the main one depends on B12 and folate, and a backup uses methyl groups from betaine, which the body makes from choline. When folate is low, the body leans more on the backup, and its need for choline rises.
↔Iron
Iron and folate are both essential raw materials for red blood cells, but their deficiencies push in opposite directions: low iron makes red cells small, while low folate or vitamin B12 stalls DNA synthesis and makes them large. When both are low, the mean cell volume (MCV) can land back in the normal range and hide both problems.
There are two routes for turning homocysteine back into methionine: one depends on folate and vitamin B12, and in the other betaine (TMG) hands over a methyl group directly. When the demand for methylation is high, the two routes run in parallel, and neither replaces the other.
cofactor · 4
B12 and folate work together in one reaction: turning homocysteine back into methionine, which feeds methylation throughout the body and supplies material for making DNA. A shortage of either one makes red blood cells large and few. High-dose folic acid can correct that anemia yet cannot stop the nerve damage of B12 deficiency, so the cause of the anemia has to be found first.
The active form of vitamin B6 (PLP) is the coenzyme for two key reactions: one takes a one-carbon unit off serine and hands it to folate, and the other sends homocysteine toward making cysteine. So in one-carbon metabolism, folate and B6 stand on two sides of the same junction.
The neural tube closes 21–28 days after conception, before most people know they are pregnant. Cells in the embryo divide extremely fast in those weeks, and the building blocks of their DNA come from folate-dependent one-carbon metabolism, which is why folic acid needs to start before pregnancy.
Glycine is an important source of one-carbon units: when it is broken down or converted, it hands one carbon to folate for making DNA and for methylation.
antagonism · 1
↮Zinc
Some studies have suggested that folic acid at supplement doses may slightly lower zinc absorption, but the results disagree and the effect is small; most people do not need to change how they take them.
depletes · 2
Long-term drinking drains folate in several ways: it blocks absorption in the gut, increases loss through the kidneys and disrupts one-carbon metabolism in the liver. Alcohol combined with low folate raises homocysteine and throws DNA methylation off, which is thought to speed up alcoholic liver damage. Drinking in pregnancy is especially dangerous, and low folate adds to the risk of neural-tube defects.
The neural tube closes about 24–28 days after conception, a time of very fast cell division, and folate supplies the one-carbon units needed to make DNA. Many people do not yet know they are pregnant at that point, so the US Preventive Services Task Force (USPSTF) recommends that everyone planning or able to become pregnant take 400–800 µg of folic acid a day, starting before pregnancy rather than at the first prenatal visit.
regulates · 1
In a fatigue work-up, folate deficiency and B12 deficiency should be checked together: they look alike on blood tests, and taking folate alone can hide the anemia of B12 deficiency while nerve damage keeps progressing behind a normal blood count.